Current clinical opinion on CFTR dysfunction and patient risk of pancreatitis: diagnostic and therapeutic considerations.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride and bicarbonate secretion is integral to the pancreas' ability to produce the alkaline pancreatic juice required for proper activation of enzymes for digestion. Disruption in this process increases the risk for pancreatitis. AREAS COVERED: Using original basic and clinical research, as well as clinical case reports and recent reviews indexed in PubMed, we discuss why patients with CFTR dysfunction are at risk for pancreatitis. We also discuss diagnostic modalities for assessing CFTR function, as well as new therapeutic advancements and the impact these are having on pancreatic function, pancreatitis in particular. EXPERT OPINION: CFTR-related pancreatitis occurs in the presence of monallelic or biallelic mutations and/or from toxin-mediated channel disruption. Research-based CFTR diagnostics have been expanded, yet all current methods rely on measuring CFTR chloride transport in non-pancreatic cells/tissue. Newer CFTR-directed therapies ('CFTR modulators') are both improving pancreatitis (pancreatic-sufficient CF patients) and increasing the risk for pancreatitis (previously pancreatic-insufficient CF patients). Our experiences with these drugs are enlightening us on how CFTR modulation can affect pancreatitis risk across a wide spectrum of pancreatic disease, and represents an opportunity for therapeutic relief from pancreatitis in those without CF, but who suffer from CFTR-related pancreatitis.